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O uso de genes em terapias é um conceito originado em 1970 em consequência do crescimento exponencial de novas tecnologias para liberação de DNA, também pela capacidade de expressão de genes exógenos em células de mamíferos. Propomos, então, a síntese de polímeros catiônicos, em dois grupos, por meio da aminólise da poli(succinimida) (PSI): grupo 1An, polímeros catiônicos com arcabouço poli (ácido aspártico) com cadeias laterais contendo aminas protonáveis; grupo 2An, polímeros catiônicos anfifílicos, contenho o poli (ácido aspártico) como arcabouço, com aminas protonáveis e cadeias dodecilamina. Estudos de SEC mostraram que derivados dodecilados 2An tiveram tamanho menor que os polímeros do grupo 1An, não dodecilados. A capacidade tamponante para todos os polímeros sintetizados foi maior que o bPEI 25, e o grupo 2An apresentou as maiores capacidades tamponantes. Derivados 2An com as aminas A1 a A4 apresentaram menor CMC do que o grupo 1An. Citotoxicidade dos policátions foi dependente das suas concentrações e, entre todos os polímeros, aqueles com aminas A5 e A6 não foram citotóxicos. A presença da cadeia dodecilamina na PSI não diminuiu a viabilidade celular até 250 ?L-1, sugerindo que a porção hidrofóbica não é citotóxica na faixa de concentrações testada. A complexação do pEGFP-N3 com os derivados de PSI foi realizada, bem como a transfecção dos poliplexos em células HeLa. A expressão de GFP dos complexos obtidos com bPEI 25 foi quantificada e comparada com os poliplexos preparados com os derivados da PSI. Ensaios de transfecção mostraram que os derivados dodecilados da PSI apresentaram expressão negligenciável de GFP em células HeLa, sugerindo uma ligação forte entre plasmídeo e os derivados sintetizados e não-liberação do material genético nas células, ou dano celular causado pela cadeia hidrofóbica nas células. Os maiores valores de GFP quantificados foram encontrados nos poliplexos contendo polímeros não-dodecilados e com as aminas A3 e A4, nas razoes N:P 5 a 20 para A3 e N:P 5 para A4. Ambas as estruturas A3 e A4 fazem parte do core do bPEI 25. / Genes as drugs for human therapy is a concept originally conceived around 1970, a consequence of the exponential growth in knowledge of human gene function, the more effective technologies for DNA delivery, and the ability to transfer and express exogenous genes in mammalian cells. Here we propose synthesizing two small library groups of cationic polymers via aminolysis of poly(succinimide) (PSI) backbone: group 1An, polycationic polymers with a degradable amide of poly(aspartic) acid backbone, protonable oligoamine side chains into the main polymer structure, and group 2An, amphiphilic cationic polymers with a degradable amide of poly(aspartic) acid backbone, protonable oligoamine side chains into the main polymer structure and dodecyl side chain moieties. SEC showed that dodecylated derivatives 2An had lower size than 1An group, non-dodecylated polyelectrolytes. Buffering capacity of all synthesized polymers was higher than the standard bPEI 25, and the dodecylated 2An group had the highest buffering capacities values. 2An derivatives with amines A1 to A4 showed lower CMC than their non-dodecylated pairs. Cytotoxicity of all polycations was dependent on the concentrations, and among all polymers, those with amines A5 and A6 had lower cytotoxicity than bPEI 25. Moreover, the presence of the hydrophobic dodecyl side chain in the PSI backbone did not decrease the cell viability until 250 ?g mL-1 polymer concentration, thus suggesting the hydrophobic moiety is not cytotoxic in this range. Complexation of pEGFP-N3 plasmid with PSI derivatives grafted with amines A1 to A4 was performed, as well as the transfection of polyplexes into HeLa cells. GFP expression of bPEI25 polyplexes in different complex volumes was quantified and compared with PSI derivatives/pEGFP-N3 polyplexes. Transfection assays showed that dodecylated PSI derivatives had negligible or no GFP expression in HeLa cells, thus suggesting a strong interaction between polycations and pDNA or a cellular damage caused by the hydrophobic moiety, although cytotoxicity assay of polyplexes showed low cytotoxicity of polyplexes. The highest GFP expression values were found for polycations 1A3 and 1A4, both without the dodecylamine side chain, in the N:P ratios 5 to 20 for 1A3, and N:P ratio 5 for 1A4. Both amines A3 and A4 used for the PSI grafting are core structures of bPEI 25.

The use of inexpensive metal catalysts for a range of acylation reactions including the activation of anhydrides and the aminolysis of esters. Discussion on the use of a heterogeneous copper catalyst for teh reduction of a range of organic functional groups and its use in amination of nitriles.

This diploma thesis dealt with the comparison of different methods of amination of polycaprolcatone in terms of their effectiveness for tissue engineering. A polycaprolactone membrane was prepared by an electrospinning method, which was subsequently modified by three different amination methods. Selected types of amination were plasma polymerization with cyclopropylamine monomer, hybrid modification using plasma and N-allylmethylamine monomer, and chemical amination using aminolysis with diaminohexane. Surface amines were subsequently characterized by electron scanning microscopy (SEM), X-ray photoelectron spectroscopy (XPS), attenuated total reflection infrared spectroscopy (ATR-FTIR) and contact angle measurement. A cell culture designated A375 (Human malignant melanoma cell lines A375® CRL-1619®) was cultured on the thus modified membranes, which was analyzed by optical microscopy, and a proliferation assay was performed by determining the relative amount of ATP. Based on the experimental results, we can confirm the success for all types of amination. In terms of efficiency for tissue engineering, the amination method by plasma polymerization with the monomer cyclopropylamine has the most satisfactory results.

Tesis por compendio / [ES] El uso masivo de plásticos sintéticos y su impacto medioambiental obliga a buscar alternativas biodegradables para el envasado de los alimentos,etapa necesaria para su adecuada conservación.Así mismo,la necesidad de incrementar la vida útil de los alimentos ha despertado gran interés en el desarrollo de materiales activos(antimicrobianos y antioxidantes)que mantengan su calidad y seguridad por más tiempo,mediante el uso de compuestos de origen natural,seguros para el consumidor.En este sentido,el desarrollo de materiales biodegradables activos para el envasado de alimentos constituye hoy en día un reto importante para la industria alimentaria.En la presente Tesis Doctoral,se ha estudiado la encapsulación de carvacrol mediante el electroestirado o extensión y secado de diferentes disoluciones poliméricas con carvacrol.Se han utilizado polímeros biodegradables portadores de diferente polaridad(almidón termoplástico:TPS,polivinil-alcohol:PVA, policaprolactona:PCL o ácido poliláctico:PLA)disueltos en el solvente adecuado,con el fin de obtener capas activas.Estas capas se han combinado con otras de polímeros con propiedades complementarias,para obtener laminados activos adecuados para el envasado de alimentos.Los laminados combinaron polímeros polares(TPS o PVA)y poliésteres no polares(PCL o PLA)incorporando el carvacrol en una de las capas.Se evaluó la cinética de liberación del activo,así como la acción antimicrobiana de los materiales obtenidos.Los laminados se caracterizaron en su funcionalidad como material de envase(prop. de barrera,mecánicas u ópticas)así como en su estructura y comportamiento térmico.Los estudios de encapsulación revelaron un mayor potencial encapsulante del carvacrol para los polímeros no polares(PCL;PLA),aunque el PVA mostró también una buena afinidad con el compuesto activo.La matriz de PVA mostró una mayor retención de carvacrol mediante electroestirado de sus disoluciones acuosas que por extensión y secado,sin necesidad de adición de tensoactivos como el Tween85.Para la encapsulación en PLA,se usaron mezclas binarias de solventes aptos para contacto con los alimentos(acetato de etilo y DMSO).En este caso,se obtuvo una mayor eficiencia encapsulante del PLA en los materiales obtenidos por extensión y secado que en los electroestirados.La cinética de liberación del carvacrol de las fibras de PCL explicó el mayor efecto antibacteriano contra E.coli,y el escaso efecto antilisteria.La velocidad de liberación del activo aumentó cuando disminuyó la polaridad de los simulantes alimentarios, mostrando una liberación completa en los sistemas apolares,pero solo hasta 75% en los sistemas acuosos,que requerirían una mayor proporción del activo en el envase para potenciar su efectividad.La combinación de láminas de TPS con fibras de PCL cargadas con carvacrol dio lugar a materiales con una permeabilidad al vapor de agua mejorada,en comparación con los films de almidón,sin efectos relevantes sobre las otras propiedades funcionales estudiadas.Cuando los laminados se probaron in vitro contra cepas G(+) y G(-) mostraron un efecto antibacteriano similar al de las fibras de PCL con carvacrol,pero retrasado en el tiempo.Los estudios de desintegración-biodegradación de los laminados almidón-PCL revelaron que las películas con carvacrol afectaron la actividad del inóculo del compost,disminuyendo ligeramente la biodegradabilidad de las películas,pero alcanzando valores de desintegración similares(75-80%)a las muestras libres de carvacrol.Se obtuvieron también laminados de PLA y PVA mediante la extensión y secado de disoluciones acuosas de PVA con carvacrol.La superficie del PLA fue sometida a aminolización a fin de mejorar la extensibilidad de las disoluciones acuosas.A pesar del incremento de la componente polar de la energía superficial del PLA y su mejorada humectabilidad con las soluciones de PVA,estas bicapas no mostraron una mejora significativa en las propied / [CA] L'ús massiu de plàstics sintètics i el seu impacte mediambiental obliga a buscar alternatives biodegradables per a l'envasament dels aliments necessari per a la seua conservació.Així mateix,la necessitat d'incrementar la vida útil dels aliments ha despertat gran interés en el desenvolupament de materials actius(antimicrobians i antioxidants)que mantinguen la seua qualitat i seguretat per més temps,per mitjà de l'ús de compostos d'origen natural,segurs per al consumidor.En este sentit,el desenvolupament de materials biodegradables actius per a l'envasament d'aliments constituïx un repte important per a la indústria alimentària.En la present Tesi Doctoral,s'ha estudiat l'encapsulació de carvacrol per mitjà de l'electroestirat o extensió i assecat de diferents dissolucions polimèriques amb carvacrol.S'han utilitzat polímers biodegradables portadors de diferent polaritat(midó termoplàstic:TPS, polivinil-alcohol:PVA, policaprolactona:PCL o àcid poliláctic:PLA)dissolts en el solvent adequat,a fi d'obtindre capes actives.Estes s'han combinat amb altres de polímers amb propietats complementàries,per a obtindre laminats actius adequats per a l'envasament d'aliments.Els laminats van combinar polímers polars(TPS o PVA)i poliésters no polars(PCL o PLA)incorporant el carvacrol en una de les capes.Es va avaluar la cinètica d'alliberament de l'actiu,així com l'acció antimicrobiana dels materials obtinguts.Els laminats es van caracteritzar en la seua funcionalitat com a material d'envàs(propietats de barrera, mecàniques o òptiques),així com en la seua estructura i comportament tèrmic.Els estudis d'encapsulació van revelar un major potencial encapsulant del carvacrol per als polímers no polars(PCL i PLA),encara que el PVA va mostrar també una bona afinitat amb el compost actiu.La matriu de PVA va mostrar una major retenció de carvacrol per mitjà d'electroestirat de les seues dissolucions aquoses que per extensió i assecat,sense necessitat d'addició de tensioactius com el Tween 85.Per a l'encapsulació en PLA,es van usar mescles binàries de solvents aptes per a contacte amb els aliments(acetat d'etil i DMSO).Es va obtindre una major eficiència encapsulant del PLA en els materials obtinguts per extensió i assecat que en els electroestirats.La cinètica d'alliberament del carvacrol de les fibres de PCL va explicar el major efecte antibacterià contra Escherichia coli,i l'escàs efecte antilisteria.La velocitat d'alliberament de l'actiu va augmentar quan va disminuir la polaritat dels simulants alimentaris,mostrant un alliberament complet en els sistemes no polars, però només fins a un 75% en els sistemes aquosos,que requeririen una major proporció de l'actiu en l'envàs per a potenciar la seua efectivitat.La combinació de làmines de TPS amb fibres de PCL carregades amb carvacrol va donar lloc a materials amb una permeabilitat al vapor d'aigua millorada,en comparació amb els films de midó, sense efectes rellevants sobre les altres propietats funcionals.Quan els laminats es van provar in vitro contra ceps Gram(+) i Gram(-) van mostrar un efecte antibacterià semblant al de les fibres de PCL amb carvacrol,però retardat en el temps.Els estudis de desintegració-biodegradació dels laminats midó-PCL van revelar que les pel·lícules amb carvacrol van afectar l'activitat de l'inocule del compost,disminuint lleugerament la biodegradabilitat,però aconseguint valors de desintegració semblants(75-80%)a les mostres lliures de carvacrol.Es van obtindre també laminats de PLA i PVA per mitjà de l'extensió i assecat de dissolucions aquoses de PVA amb carvacrol.La superfície del PLA va ser sotmesa a aminolizatció a fi de millorar l'extensibilitat de les dissolucions aquoses.A pesar de l'increment de la component polar de l'energia superficial del PLA i la seua millorada mullabilitat amb les solucions de PVA,estes bicapes no van mostrar una millora significativa en les propietats mecàniques i de barrera / [EN] The massive use of synthetic plastics and their environmental impact makes necessary the search for biodegradable alternatives for food packaging. Likewise, the need to increase the shelf life of food has aroused great interest in the development of active materials (antimicrobial and antioxidant) that maintain food quality and safety for longer periods of time through the use of compounds of natural origin, safe for the consumer. In this sense, the development of active biodegradable materials for food packaging is both a major imperative and challenge for the food industry today. In the present Doctoral Thesis, the encapsulation of carvacrol has been studied by means of the electrospinning or casting of different polymeric solutions with carvacrol. Biodegradable polymers with different polarities (thermoplastic starch: TPS, poly(vinyl-alcohol): PVA, poly-(¿-caprolactone): PCL or poly(lactic acid): PLA) dissolved in the appropriate solvent have been used to obtain active layers. These have been combined with other polymers with complementary properties, to obtain active laminates suitable for food packaging. The laminates combined polar polymers (TPS or PVA) and non-polar polyesters (PCL or PLA) incorporating carvacrol in one of the layers. The release kinetics of the active ingredient was evaluated, as well as the antimicrobial action of the materials obtained. The laminates were characterized in their functionality as a packaging material (barrier, mechanical or optical properties), as well as in their structure and thermal behaviour. Encapsulation studies revealed a higher encapsulating potential of carvacrol for non-polar polymers (PCL and PLA), although PVA also showed a good affinity with the active compound. The PVA matrix showed a higher retention of carvacrol by electrospinning of its aqueous solutions than by casting, without the need for addition of surfactants such as Tween 85. For the encapsulation in PLA, binary mixtures of solvents suitable for food contact (ethyl acetate and DMSO) were used. A higher encapsulation efficiency of PLA was obtained in the materials produced by casting than by electrospinning. The carvacrol release kinetics of PCL fibres explained the higher antibacterial effect against Escherichia coli and the lower antilisterial effect. The release ratio of the active ingredient increased when the polarity of the food simulants decreased, showing a complete release in non-polar systems and only up to 75% in aqueous systems that would require a higher proportion of the active ingredient in the packaging material to enhance its effectiveness. The combination of TPS films with carvacrol loaded PCL fibres resulted in materials with improved water vapour permeabilities, compared to starch films, with no relevant effects on the other functional properties. When the laminates were tested in vitro against Gram (+) and Gram (-) strains, they showed a similar antibacterial effect to that of PCL fibres with carvacrol, but delayed in time. Disintegration-biodegradation studies of PCL-starch laminates revealed that carvacrol films affected the activity of the compost inoculum, slightly decreasing the biodegradability of the laminates, but reaching similar disintegration values (75-80%) to the carvacrol-free samples. PLA and PVA laminates were also obtained by casting aqueous PVA solutions with carvacrol. The surface of PLA was submitted to aminolization in order to improve the extensibility of the aqueous solutions. Despite the increase in the polar component of the PLA surface energy and its improved wettability with PVA solutions, these bilayers did not show significant improvement in mechanical and barrier properties over the PLA monolayers. / The authors would like to thank the Ministerio de Economia y Competitividad of Spain, for funding this study as part of projects AGL2013-42989-R and AGL2016-76699-R and predoctoral research grant # BES-2014-068100. / Tampau, A. (2020). Carvacrol encapsulation by electrospinning or solvent casting to obtain biodegradable multilayer active films for food packaging applications [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/140313 / TESIS / Compendio

Grafenoxid (GO) ar en lovande kandidat som nano-tillsats i medicinska byggnadsstallningar for benregenerering. GO kan forbattra den biologiska kompatibiliteten och osteogena prestandan hos polymerbaserade byggstallningar, och ocksa vasentligt bidra till forbattringen av materialets mekaniska egenskaper. I detta arbete ympades nano-grafenoxid (nGO) kovalent pa ytan av poly (e-kaprolakton) (PCL) genom att fdrst modifiera polymerytan via aminolys. Med anvandning av 1,6-hexandiamin / isopropanol infordes fria amingrupper framgangsrikt pa PCL-ytan for efterfoljande immobilisering av nGO. En optimerad ympningsprocess utvecklades via en losningsmedelsassisterad metod med vatten som losningsmedel for att kovalent binda nGO pa ytan av PCL byggnadsstallningar. De initiala nGO koncentrationerna var 0,5 och 1 mg / ml. fourier-transform infrarodspektroskopi (FTIR) och termogravimetrisk analys (TGA) verifierade bindningen mellan de funktionella gruppema pa nGO och de fria aminema. Svepelektronmikroskopi (SEM) visade en homogen fordelning av nGO pa ytan av de porosa byggnadsstallningarna. De mekaniska testema som utfordes demonstrerade · en 50 och 21 % okning av kompressionsstyrkan :for byggnadsstallningarna ympade med de initiala nGO-koncentrationema pa 0,5 och 1 mg / ml. In vitro-mineraliseringstester visade bildandet av mineralfallningar pa ytan av byggnadsstallningama som okade i storlek med hogre nGO-halt. A ven nGO: s potential som nano-barare av ett antibiotikum studerades i detta arbete. Pa grund av sitt overflod av kemiska funktionaliteter kan nGO effektivt adsorbera foreningar genom olika sekundara interaktioner. I denna studie optimerades dessa sekundara interaktioner genom att reglera losningens pH for maximal adsorption av ciprofloxacin, ett bredspektrum antibiotikum som anvands vid behandling av osteomyelit. Ciprofloxacin befanns kunna adsorberas starkast i sin katjonform vid pH 5, dar 1t-1t elektron­donatoracceptor (EDA) -interaktioner dominerar. Sammanfattningsvis bekraftar de resultat som presenteras i detta arbete potentialen hos nGO som egenskapsforbattrare och lakemedelsbarare i applikationer inom vavnadsregenerering. / Graphene oxide (GO) is a promising candidate as nano-filler material in scaffolds for bone regeneration. It has been demonstrated to enhance the biological compatibility and osteogenic performance of polymer-based scaffolds, aside from its substantial contribution to the improvement of the material's mechanical properties. In this work, nano-graphene oxide (nGO) was covalently grafted to the surface of poly( e-caprolactone) (PCL) by first modifying the polymer surface via aminolysis. Using 1,6-hexanediamine/isopropanol, free amine groups were successfully introduced to the PCL surface for the subsequent immobilization of nGO. An optimized grafting pathway, which implements the solvent-assisted method and uses water as a solvent, was developed to covalently attach nGO using initial concentrations of 0.5 and 1 mg/mL. Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) both verified the successful attachment of nGO through the free amines. Scanning electron microscopy (SEM) depicts a homogeneous dispersion of nGO over the polymer matrix. Mechanical tests were performed and demonstrate a 50 and 21 % increase in compressive strength for the scaffolds grafted using initial nGO concentrations of 0.5 and 1 mglmL. In vitro mineralization tests showed the formation of mineral precipitates on the surface of the scaffolds that increased in size with higher nGO content. The potential of nGO as a nano-carrier of an antibiotic drug was also explored in this work. As it comprises of an abundance of chemical functionalities, nGO is able to efficiently adsorb compounds through various secondary interactions. In this study, these secondary interactions were optimized by controlling the solution pH for the maximum adsorption of ciprofloxacin, a broad-spectrum antibiotic used in the treatment of osteomyelitis. Ciprofloxacin was found to be adsorbed most strongly in its cationic form at pH 5, in which 1t-1t electron-donor acceptor (EDA) interactions predominate. Overall, the results presented in this work validate the potential of nGO as nano-enhancer and drug carrier in tissue engineering scaffold applications.

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-05-09T17:53:03Z No. of bitstreams: 1 camilaguimaraesdealmeida.pdf: 4348908 bytes, checksum: 2103ec3e5867e67082b5aeed5c341eba (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-05-17T14:31:51Z (GMT) No. of bitstreams: 1 camilaguimaraesdealmeida.pdf: 4348908 bytes, checksum: 2103ec3e5867e67082b5aeed5c341eba (MD5) / Made available in DSpace on 2017-05-17T14:31:51Z (GMT). No. of bitstreams: 1 camilaguimaraesdealmeida.pdf: 4348908 bytes, checksum: 2103ec3e5867e67082b5aeed5c341eba (MD5) Previous issue date: 2014 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / As N-aciletanolaminas graxas, assim como seus derivados, são encontradas com frequência na natureza. Pertencem a uma classe de compostos não iônicos amplamente utilizados por suas propriedades surfactantes em detergentes e xampus, bem como em formulações cosmético-farmacêuticas. O uso de matéria-prima renovável obtida a partir de resíduos industriais se mostra uma alternativa interessante para a síntese destas moléculas. As sementes de maracujá, subprodutos da indústria alimentícia, são ricas em triacilgliceróis que podem originar amidas graxas através de reações de aminólise direta ou indireta. Neste trabalho são descritas a síntese de misturas contendo amidas graxas obtidas a partir do tratamento do óleo de maracujá com três diferentes aminas na presença de catalisadores químicos heterogêneos e homogêneos, bem como irradiação de micro-ondas. Os catalisadores heterogêneos selecionados, descritos na literatura para reações de transesterificação, mostraram-se eficientes em reações de aminólise direta e indireta. A otimização das condições reacionais (modo de aquecimento, quantidade de catalisador, tempo reacional) mostrou que o óxido misto ZnO.La2CO5.LaOOH (2,3 % m/m) foi o que apresentou as maiores conversões (>99%) em menor tempo reacional (8 h). O ácido p-sulfônico calix[4]areno previamente descrito para reações de esterificação de ácidos graxos, mostrou-se eficaz em reações de transesterificação (96-99% de conversão) e aminólise direta de triglicerídeos (50->99% de conversão). Após caracterização dos óleos e das misturas de amidas graxas através dos métodos espectroscópicos usuais (RMN de 1H, RMN de 13C e IV) suas propriedades biológicas foram avaliadas in vitro. Os óleos vegetais apresentaram atividade antioxidante atribuída à presença de tocoferóis e ao alto índice de insaturação dos triglicerídeos presentes. As misturas também foram avaliadas quanto ao potencial antibacteriano e antifúngico. Apenas a mistura de N’N’-dimetiletilenodiamida graxa apresentou atividade frente a quatro cepas de Candida sp. testadas (CIM = 32-128 µg/mL). A incorporação das misturas de amidas graxas em cremes e sabonetes está em estudo. / Fatty N-aciletanolamines, as well as their derivatives, are frequently found in nature. They belong to a class of nonionic compounds widely used for their surfactant properties in detergents and shampoos, as well as in cosmetic and pharmaceutical formulations. The use of renewable raw materials obtained from industrial wastes appears as an interesting alternative for the synthesis of these molecules. Passion fruit seeds, subproducts of the food industry, are rich in triacylglycerols that can originate fatty amides through reactions of direct or indirect aminolysis. In this work we describe the the synthesis fatty amide mixtures obtained through the treatment of passion fruit oil with three different amines in the presence of heterogeneous chemical catalysts or under microwave irradiation. The selected heterogeneous catalysts, previously reported in the literature for transesterification reactions, proved to be effective in direct and indirect aminolysis. The optimization of the reaction conditions (heating mode, amount of catalyst, reaction time) showed that the mixed oxide ZnO.La2CO5.LaOOH (2.3%, w/w) led to the highest conversions (>99%) in a shorter time (8 h). The calix [4]arene p-sulfonic acid previously described for the esterification of fatty acids, was effective in transesterification reactions (96-99 % conversion) and direct aminolysis of triglycerides (50- >99% conversion). After the characterization of passion fruit oils and of the fatty amides mixtures using the usual spectroscopic methods (1H and 13C NMR, IR) their biological properties were evaluated in vitro. The vegetable oils showed antioxidant activity attributed to the presence of tocopherols and to the high index of unsaturation of the present triglycerides. The mixtures were also evaluated for their antibacterial and antifungal potential. The mixture of fatty N'N'-dimetiletilenodiamide mixture was the only one to display activity against the four strains of Candida sp. tested (MIC = 32-128 µg/ml). The incorporation of fatty amides mixtures in creams and soaps are under study.

Les tétrahydropyranes et les pipéridines sont des motifs que l'on retrouve dans de nombreuses molécules naturelles bioactives. L'intérêt pour ces familles de composés ne cesse de croître. En effet le noyau pipéridine est le troisième motif cyclique le plus retrouvé dans les molécules thérapeutiques après les noyaux phényle et pyridine alors que le tétrahydropyrane prend lui la 6ème place. Il apparaît donc opportun de développer des voies d'accès simples et efficaces afin d'obtenir de façon stéréosélective (diastéréo et/ou énantiosélective) ces motifs structuraux. Les travaux de recherche présentés dans ce manuscrit concernent le développement de deux nouvelles méthodologies de la cyclisation d'aza-Prins. La cyclisation d'aza-Prins permet par la réaction entre une amine homoallylique et un aldéhyde en présence d'un acide (Lewis ou Brønsted) la formation de pipéridine. La première a été développée pour pallier à l'absence dans la littérature de méthodologie applicable à tous types d'amines homoallyliques. Cette nouvelle méthodologie repose sur la promotion de la réaction par un effet synergétique entre un acide de Lewis (TiCl4 1 éq.) et un acide de Brønsted (p-TSA 0.1 éq.). Cette méthodologie a permis l'obtention de pipéridine avec de bons rendements et une excellente diastéréosélectivité a été obtenue selon la nature de l'amine homoallylique utilisé. La deuxième méthodologie qui a été développée permet l'aminolyse de pipéridine-lactone. Ces pipéridine-lactones, obtenues par une réaction d'aza-Prins, sont ainsi aminolysées par un acide aminé en présence d'un promoteur puissant LiNTf2. Ces deux méthodologies combinées nous ont permis d'obtenir divers motifs pipéridines. Un certain nombre de ces pipéridines synthétisées seront testées afin de mettre en évidence une éventuelle activité biologique. / Tetrahydropyrans and piperidines are cyclic motifs found in numerous bioactive natural products. Interest in these families of compounds is continuously growing. Indeed, piperidine is the 3rd most common cyclic motif found in therapeutic molecules after phenyl and pyridine structures, while the tetrahydropyran takes the 6th place. Thus the development of simple and effective methodologies to obtain these structures stereoselectively (diastereo and/or enantioselectively) is of great interest. The research presented in this manuscript concerns the development of two new methodologies for aza-Prins cyclization. These reactions involve condensation of homoallylic amines with aldehydes in the presence of a Lewis or Brønsted acid to give piperidine compounds. The first method was promoted by a synergistic combination of a Lewis acid and a Brønsted acid and employs N-alkyl, N-aryl, and unprotected homoallylamines to efficiently form piperidines with good yields and excellent diastereoselectivity, which was controlled by the nature homoallylamine. The second method allows piperidine-lactone aminolysis in presence of aminoacids with the help of a powerful promoter LiNTf2. These two combined methodologies allowed us to obtain a library of piperidine structures, some of which will be tested in order to assess their possible biological activity.

Des nouvelles voies de synthèse sont proposées pour la préparation des hydroxyuréthanes et polyhydroxyuréthanes glycériliques, sans isocyanate, à partir de composés biosourcés fournisseurs de groupements cyclocarbonates hautement réactifs vis-à-vis des amines, diamines, polyamines. Les fournisseurs de groupement cyclocarbonate sont le carbonate de glycérol et le nouveau synthoon bifonctionnel l’acrylate de carbonate de glycérol. Des hydroxyuréthanes ou polyhydroxyuréthanes glycéryliques polyoxygénés et polyazotés ont été ainsi élaborés via ces nouveaux intermédiaires cyclocarbonates glycériliques en substitution des carbonates cycliques d’origine fossile comme les carbonates d’alkylènes. La stratégie d’élaboration des polyhydroxyuréthanes glycériliques à haut poids moléculaire s’appuie sur la réactivité séquencée de l’acrylate de carbonate de glycérol : réaction d’Aza-Michaël sur le groupement éthylénique de l’acrylate et réaction d’aminolyse par ouverture de cycles carbonates à 5- chaînons. Selon la nature des polyamines, on prépare des polymères de poids moléculaire supérieur à 40000 g/mol, d’aspects gel, mousse ou résine selon que les pontages linéaires ou interchaînes prédominent. Des réseaux chimiques intramoléculaires sont constitués par l’établissement des liaisons hydrogène entre les sites O-H ou N-H et l’oxygène du groupement carbamoyle du squelette glycérilique avec comme conséquence la réduction de la susceptibilité du groupe carbamoyle à l’hydrolyse et l’amélioration des propriétés de résistance chimique et mécanique des polyhydroxyuréthanes glycériliques. / New synthesis routes have been developed for the preparation of glycerilic hydroxyurethanes and polyhydroxyurethanes without the use of isocyanates. They were prepared from biosourced cyclocarbonates, highly reactive towards amines, diamines and polyamines. The providers of cyclocarbonate function are glycerol carbonate and glycerol acrylate carbonate which is a bifunctional reactive. Glycerilic hydroxyurethanes and polyhydroxyurethanes with high oxygenated and nitrogenated potential were then designed via these new glycerilic cyclocarbonates’ intermediates, substitutes of fossil cyclic carbonates such as ethylene or propylene carbonates. The strategy development of high molecular weights glycerilic polyhydroxyurethanes is based on the sequenced reactivity of the glycerol acrylate carbonate: Aza-Michaël reaction on the ethylenic function of the acrylate and aminolysis reaction of the 5-membered cyclic carbonate function. According to the nature of the amine, polyhydroxyurethanes up to 40,000 g/mol were obtained. They can be obtained as foams, gels, resins, depending on the predominance of linear or cross-linked bridges. Intramolecular chemical networks were elaborated by hydrogen bonding between O-H or N-H sites with the oxygen atom of the carbamoyl function of the glycerilic skeleton. That is the reason why carbamoyle functions are less susceptible to hydrolysis and why the chemical and mechanical resistance properties of the glycerilic polyhydroxyurethanes are increased.

Nesta dissertaçao foram estudadas as reações de aminólise de benzoatos por dodecilamina (DA), propionato de dodecilamôrtio (DAP) e suas misturas em ciclohexano. Foram usados os ésteres do tipo X-Ø-CO2-Ø-NO2 (X=NO2,CH3O,CH3,H e Cl) e NO2-Ø-CO2-Ø-Y (Y=CH3 , H, Cl e CN). A aminólise de ésteres por DA é de segunda ordem em amina e está associada com entropias de ativação altamente negativas e pequenas eutalpias de ativação. A reação é muito mais sensível à natureza do grupo abandonador que da acila. Na reaçao com DAP micelar mostrou-se claramente que o grupo carboxilato de detergente atua com base geral e não como nucleófilo. A reação é de segunda ordem em DAP e apresentou as mais altas entropias de ativação. O valor de ρ de Hammett era maior quando se variou o grupo Y, mostrando que a reação, como com DA, é mais sensível à natureza do grupo fugitivo. O valor da razão ρY/ρX mostrou que o grupo abandonador é o íon fenóxido p-substituido. Uma prova adicional deste fato, foi obtida dos resultados de aminólise em presença de água solubilizada. O DAP micelar aumentou a velocidade de aminólise por DA, por fatôres desde 132 vêzes (Cl/NO2) até 311 vêzes (NO2/NO2 ). A aminólise de ésteres por DA+DAP apresentou parâmetros de ativação, cujos valores são intermediários àqueles para as reações com DA e com DAP respectivamente. Os valores de ρ de Hammett foram similares aqueles obtidos para a reação com DAP somente. Baseados nos resultados previamente reportados, foram sugeridos esquemas para as reações. Eles envolvem a formação de intermediários tetraédricos (aniônicos para as reações com DA e com DAP e zwitteriônicos para a aminólise por DAP), cujo colapso é determinante da velocidade. / In this thesis the aminolysis of benzoate esters by dodecylamine (DA), dodecylammonium propionate (DAP) and their mixtures in cyclohexane was studied. The esters used were X-ØCO2ØNO2 (X=NO2CH3O,CH3,H e Cl) and NO2ØCO2ØY (Y=CH3,H,Cl e CN). Ester aminolysis by DA is second order in the amine and is associated with a highly negative entropies and small euthalpies of activation. The reaction is much more sensitive to the nature of the leaving group than that of the acyl one. In the reaction with micellar DAP it was clearly showed that the carboxylate group of the surfact and is acting as a general base, not as a nucleophile. The reaction was found to be second order in the surfactant and showed the highest entropies of activation. The Hammett ρ value was larger when was varied, showing that the reaction, like that with DA, is more sensitive to the nature of the leaving group. From the ratio ρY/ρX it was shown that the leaving group is the P-substituted phenoxide ion. Additional proof for this was reached from the results of aminolysis in the presence of solubilized water. Micellar DAP enhance the rate of aminolysis by DA by factors ranging from 132 times (Cl/NO2) to 311 times (NO2/ NO2). Ester aminolysis by DA+DAP has activation parameters which are intermediate between those for the reactions with DA, and with DAP, respectively. The Hammett ρ values were similar to those obtained for the reaction with DAP alone. Based on the previous data schemes for the reactions were suggested. They involve the formation of tetrahedral intermediates (anions for the reaction with DA and with DA+DAP, and zwitterion for the aminolysis by DAP) whose collapse are rate limiting.